The objective of the proposed research is to investigate the development and structural plasticity of brain opioid peptidergic neurons. We will characterize the neurogenic differentiation, and post-lesion reorganization of enkephalin/dynorphin-immunoreactive (ir) neurons in the hippocampus and Beta-endorphin-ir and enkephalin-ir neurons in the hypothalamus of male and female rats. We will use long-survival 3H-tymidine autoradiography in combination with immunocytochemistry to establish the timing of the final mitosis of hippocampal and hypothalamic opioid peptidergic neurons. We will determine whether or not these neurons have adiscrete time of origin which, along with their cytochemical specificity, may serve to distinguish them as subpopulations of dentate granule cells and medial basal hypothalamic neurons. To investigate whether or not mature hippocampal opioid peptidergic neurons reorganize their synaptic fields in response to injury, we will use immunocytochemistry and histochemical techniques to examine enkephalin/dynorphin-ir neurons in the granule cell-mossy fiber system for proliferation responses to deafferentation of the dentate granule cells. Rats of both sexes will be used to determine whether or not ontogenetic differentiation or injury induced axonal remodeling of opioid peptidergic neurons is sexually dimorphic. If sex differences are observed, future studies will be aimed at investigating the role of endocrine steroids on such sex-associated patterns of growth. Together, these experiments should establish strong paradigms for studying the development and plasticity of peptidergic neurons in the CNS. Characterizing the conditions under which opioidergic neurons will demonstrate structural plasticity in males and females should be of significant benefit for understanding injury-related CNS dysfunctions in humans.